Pathological analysis of nervous system tissues remains the standard for defining neurodegenerative diseases, monitoring their progression, and evaluating the effects of experimental or therapeutic manipulations. Imaging is critical for performing neuropathological analyses and has emerged as a powerful independent approach for investigating dynamic physiological and pathophysiological processes. The proposed program project will take maximal advantage of these valuable approaches. Accurate pathological analyses requires the expert handling and preparation of cells and tissues for study and can require the skills of a trained neuropathologist to interpret the findings. Effective application of imaging approaches requires well-maintained state-of-the-art equipment, ample opportunities for education and training, and the availability of expert consultancy. The main goals of this core are to provide the resources to project leaders of this program and enable them to address their research questions efficiently and conclusively with imaging and neuropathology approaches. To accomplish these goals, the Microscopy and Neuropathology Core proposes: Aim 1, to assist program members with the fixation and processing of brain tissues and neural cultures; Aim 2, to perform routine histological staining of cells and tissues and support immunostaining required for neuropathological studies; Aim 3, to assist and train program members in the microscopic imaging and digital documentation of their imaging data; Aim 4, to provide assistance with quantitative image analysis of morphological and immunolabeling data; and Aim 5, to establish a tissue/section bank and maintain a corresponding online database with Core A that is accessible to all projects.